This research program seeks to explain the neurogenesis of respiratory pattern in mammals in terms of the biophysical, synaptic, and network properties of neurons in the central nervous system (CNS). During the award period, research will be conducted to further develop and exploit a novel system for the study of these aspects of respiratory pattern generation. This system consists of the mammalian brainstem and spinal cord in vitro and has unique properties that facilitate experimental analysis of neural mechanisms. Unlike conventional experimental approaches in vivo, the in vitro system allows routine application of most relevant neurobiological techniques to study neural pattern generation, including direct utilization of pharmacological and membrane channel probes in the CNS, and intracellular recording to determine neuronal properties. Information to be obtained from these studies is fundamental for defining CNS mechanisms responsible for respiratory homeostasis and for understanding pathologies where ventilatory failure results from dysfunction of CNS mechanisms controlling breathing.